The etiology and detailed pathophysiology of the autoimmune endocrine diseases remain unclear. We have previously conducted detailed investigations into human autoimmune thyroid disease mechanisms with an emphasis on understanding their immunological associations. The specific aims of this competing five-year renewal involve recent major advances in our understanding of the interactions between the human thyroid cell and the immune system. Specifically, we intend to: 1. Analyze the regulation of HLA Class II antigen gene expression in normal and abnormal thyroid cells. 2. Investigate HLA genomic DNa in order to detect organ-specific gene rearrangements and specific polymorphisms associated with susceptibility to autoimmune thyroid disease. 3. We shall endeavor to produce immortalized human thyroid cells by the use of hybridoma technology to provide a resource of proliferating human thyroid cells. 4. We will examine "autoprocessing" of thyroid antigens by human thyroid cells and immortalized clones to demonstrate presentation of thyroid antigen, in association with MHC Class II molecules, directly to the immune system. These studies focus directly on the interaction between human thyroid cells and the immune system by examination of genetic and functional associations. Data generated will provide new insights into autoimmune thyroid disease at a fundamental level.